Autophagy is a basic process that may go wrong in cancer, neurodegenerative diseases.

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Today's Nobel Prize in Medicine has been awarded to Japan's Yoshinori Ohsumi for his work in understanding a fundamental biological process in which the cell digests damaged or unneeded components. Termed "autophagy," or self-eating, the process allows cells to survive periods of stress or starvation or to adapt to changing conditions or needs. Failures in autophagy have been linked to both cancer and neurodegenerative diseases.

As with many past winners, Ohsumi seems to have had the right ideas at the right time. In the 1950s, earlier Nobel winner Christian de Duve identified small structures inside cells that carried lots of digestive enzymes. Others recognized that these structures were involved in situations where cells digested parts of their own internal membranes, liberating raw materials to be reused. A decade later, the term autophagy was coined, and people recognized that it was a normal process within cells.

But over the following decades, progress on understanding how it worked was slow, in part because typical complex, eukaryotic cells are filled with small bits of membrane, and partly because the process was transient, rapidly digesting the material it was fed. We knew it was occurring, but we didn't know when or how it was triggered. This left the field open to Ohsumi, who started working on it in the 1990s.

Ohsumi decided to work on yeast cells (the same yeast that makes our bread and beer) because they're simpler and genetically tractable. Here, the interior is quite a bit less complex, though it's smaller, and individual components are typically harder to identify. One exception to that is the vacuole, a large permanent structure that's filled with digestive enzymes and handles the cell's waste and toxins. In that way, it's the equivalent of the small, membrane-bound bundles of digestive enzymes that had been seen in human cells.

To show it was actually the equivalent, Ohsumi did an experiment that ended up providing him with a tremendously useful tool. He eliminated the genes for three digestive enzymes that were known to reside in the vacuole, reasoning that this would block the processing of material there. He then starved these mutant yeast, putting them under a stress that would normally cause them to digest some of the structures they could no longer support. But because of the mutations, they couldn't be digested. Instead, lots of membrane structures started accumulating inside the vacuole—so many that the defect could be seen with a standard light microscope.

This demonstrated that, in yeast, the vacuole is where autophagy happens. But more importantly, it gave Ohsumi a handle on the process itself. In his mutant yeast, autophagy fails at the very last step, when the targeted material is being digested, leading to the accumulation of material in the vacuole. If an additional mutation were to interfere with the process, then the material might never get to the vacuole in the first place. As a consequence, you would no longer see the accumulation of material in the vacuole.

Ohsumi used this as the basis of a genetic screen, eventually identifying 15 different genes that were necessary to target material for autophagy. (Notably, rather than appearing in a high-profile publication like Science or Nature, this paper ran in a smaller journal called FEBS Letters.) Since the process is potentially dangerous were it to occur in an uncontrolled manner, many of these genes are involved in regulating it. For autophagy to occur, a complex of several proteins must be assembled and interact, a process that is regulated in part by proteins that sense the cell's nutritional state.

Most of these same genes are involved in regulating autophagy in mammalian cells, and Ohsumi helped identify and characterize these. A number are critical for embryonic development, in which cells often remodel their interiors when they adopt a specific identity, like a neuron or liver cell. Others have gone on to show that the pathway he identified is just one of a number of ways that cells can target parts of themselves for destruction and recycling.

And that's where the story comes back to medicine. One of the human versions of a gene Ohsumi originally identified turns out to be mutated in many breast and ovarian cancers. Loss of either of two others from the brains of mice causes neurodegeneration. In fact, there are now a variety of human neurological diseases where autophagy has been implicated, including Alzheimer's and Parkinson's.

The knowledge that autophagy is involved doesn't always provide an obvious route to developing a therapy. But the Nobel Committee has clearly signaled many times that simply understanding the fundamental science that helps us understand a disease is worthy of recognition.